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Loss of ATG7 in Microglia Impairs UPR, Triggers Ferroptosis and Weakens Amyloid Pathology Control [scRNA-seq]

GSE286094 Mus musculus (mouse) Single-cell RNA-seq 11 samples Submitted 2025/01/30 Platform GPL24247
At a glance

Single-cell RNA-seq · mouse · 11 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart.
Organism
Mus musculus (mouse)
Samples
11 samples: 3 × Atg7-fl/fl vs 3 × Atg7-fl/fl; Cx3cr1-CreERT2 vs 3 × Atg7-fl/fl; Cx3cr1-CreERT2; 5xFAD vs 2 × Atg7-fl/fl; 5xFADGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Loss of ATG7 in microglia impairs UPR, triggers ferroptosis, and weakens amyloid pathology controlThe Journal of experimental medicine · 2025
Summary (written by the submitters)
Microglia impact brain development, homeostasis, and pathology. One important microglial function in Alzheimer’s Disease (AD) is to contain proteotoxic amyloid β (Aβ) plaques. Recent studies reported the involvement of autophagy-related (ATG) proteins in this process. Here we found that microglia-specific deletion of Atg7 in an AD mouse model impaired microglia coverage of Aβ plaques, increasing plaque diffusion and neurotoxicity.
Read the full summary ↓
Single-cell RNA sequencing, biochemical and immunofluorescence analyses revealed that Atg7 deficiency reduces unfolded protein response (UPR) while increasing oxidative stress. Cellular assays demonstrated that these changes lead to lipoperoxidation and ferroptosis of microglia. In aged mice without Aβ build-up, UPR reduction and increase oxidative damage induced by Atg7 deletion did not impact microglia numbers. We conclude that reduced UPR and increased oxidative stress in Atg7-deficient microglia lead to ferroptosis when exposed to proteotoxic stress from Aβ plaques. However, these microglia can still manage misfolded protein accumulation as they age.
Published in
Loss of ATG7 in microglia impairs UPR, triggers ferroptosis, and weakens amyloid pathology control
Cai Z, Wang S, Cao S et al. · The Journal of experimental medicine 2025 · PMID 39945772 · doi:10.1084/jem.20230173
This dataset
Open GSE286094 in finder → Find more mouse RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE286094_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1207905. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39945772) ↗
Study design
3 × Atg7-fl/fl vs 3 × Atg7-fl/fl; Cx3cr1-CreERT2 vs 3 × Atg7-fl/fl; Cx3cr1-CreERT2; 5xFAD vs 2 × Atg7-fl/fl; 5xFAD

Supports a between-group comparison across 11 samples.

How we read this: 4 replicated groups read from 11 sample titles; they account for 11 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
Datasets on a similar topic

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